Water → 6-(4-fluorophenoxy)nicotinic acid

HRID 534729Notes

Reaction equation

HRID 534729 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl[C:10]1[N:15]=[CH:14][C:13]([C:16]([O:18]C)=[O:17])=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CS(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:10]2[N:15]=[CH:14][C:13]([C:16]([OH:18])=[O:17])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 97324-FluorophenolHCID 10796Cesium carbonateHCID 254249Methyl 6-chloropyridine-3-carboxylate

Product 1

HCID 167905786-(4-fluorophenoxy)nicotinic acidYield 90%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 4-fluorophenol (96.8 g), methyl 6-chloropyridine-3-carboxylate (30 g) and cesium carbonate (285.3 g) in DMSO (875 mL) was stirred and heated to 130° C. over a period of 1.75 h then cooled overnight. The reaction mixture was reheated to ˜150° C. over a period of 1.5 h, kept at this temperature for ˜1 h, then cooled to ˜40° C. and poured into water (4 L). The aqueous solution was extracted with ether (1.0 L) then adjusted to pH7-8 by addition of 2M HCl. The solution was extracted with further ether (2×1.0 L), then adjusted to pH 2 by addition of 2M HCl causing precipitation of a solid. The precipitate was collected by filtration, washed with water and dried overnight at 40° C. in vacuo to give the title compound as a beige/pink solid (36.7 g).

Workup

  1. temperaturethen cooled overnight
  2. waitkept at this temperature for ˜1 h
  3. temperaturecooled to ˜40° C.
  4. extractionThe aqueous solution was extracted with ether (1.0 L)
  5. additionthen adjusted to pH7-8 by addition of 2M HCl
  6. extractionThe solution was extracted with further ether (2×1.0 L)
  7. additionadjusted to pH 2 by addition of 2M HCl causing precipitation of a solid
  8. filtrationThe precipitate was collected by filtration
  9. washwashed with water
  10. customdried overnight at 40° C. in vacuo

Sources & evidence

ORD record
ord-99e11e81565f43f48f5f5bd74ebc720a
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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